The lining of blood vessels is capable of releasing substances which cause smooth muscle relaxation. These substances are called endothelium- derived relaxant factors. A variety of different conditions are thought to cause dysfunction of endothelium-derived relaxant factor release. In patients undergoing cardiac catheterization, we investigated whether factors that are associated with development of coronary artery disease also cause dysfunction of the lining of blood vessels (endothelium). Increasing age, high cholesterol levels, history of high blood pressure, diabetes and smoking were correlated with the function of the blood vessels in the leg. It was found that people with multiple risk factors had depressed release of endothelium-derived relaxant factor. This suggests that exposure to multiple risk factors for atherosclerosis may lead to dysfunction of the lining of blood vessels.